Aldosterone-Stimulated Down-Regulation of Both Type I and Type II Adrenocorticosteroid Receptors in Mouse Brain Is Mediated via Type I Receptors*
- 1 August 1989
- journal article
- research article
- Published by The Endocrine Society in Endocrinology
- Vol. 125 (2) , 817-824
- https://doi.org/10.1210/endo-125-2-817
Abstract
The concentrations of type I and type I adrenocorticosteroid receptors in brain cytosol obtained from adrenalectomized-ovariectomized female mice were measured with five different assay conditions. Among the five brain regions studied, hippocampus had the highest concentration of type I receptors, whereas cerebral cortex had the highest concentration of type II receptors. The value of properly correcting for dexamethasone cross-binding to type I receptors when type II receptors are being assayed was demonstrated using type II receptor-selective ligand RU28362. A time-course study revealed a transient up-regulation of both receptor classes in most brain regions after adrenalectomy-ovariectomy, with maximal values achieved 3-5 days postsurgery and a reduction to near-intact levels by 16 days postsurgery. A single sc injection of aldosterone given to adrenalectomized-ovariectomized mice produced a profound down-regulation of type I receptors in hippocampal, cerebral cortex, hypothalamic, brain stem, and cerebellar samples, whereas it down-regulated type II receptors only in hippocampal and cerebral cortical samples. A similar injection of RU28362 failed to down-regulate type I receptors in any brain region, but it did reduce the concentration of type II receptors in all brain regions except cerebellum. The actions of aldosterone appear to be mediated solely through type I receptors, since injections of the type I receptor antagonist RU26752 prevented aldosterone-induced down-regulation of both type I and type II receptors, whereas RU26752 had no effect on the down-regulatory actions of RU28362. The ability of aldosterone to down-regulate type I, but not type II, receptors in hypothalamic, brain stem, and cerebellar samples suggests that type I and type II receptors are concentrated in separate populations of cells in these brain regions, whereas in hippocampus and cerebral cortex there is a sufficient degree of colocalization to permit type II receptor down-regulation via the action of aldosterone-type I receptor complexes. We speculate that this action is mediated at least in part at the genomic level by the suppression of type I and type II receptor mRNA synthesis brought about by the interactions of transformed aldosterone-type I receptor complexes with the DNA regulatory elements upstream from the genes for these receptors.This publication has 40 references indexed in Scilit:
- Stress Down-Regulates Corticosterone Receptors in a Site-Specific Manner in the Brain*Endocrinology, 1984
- Renal mineralocorticoid receptors and hippocampal corticosterone-binding species have identical intrinsic steroid specificity.Proceedings of the National Academy of Sciences, 1983
- In vitro measurement of cytosol and cell nuclear androgen receptors in male rat brain and pituitaryBrain Research, 1983
- A comment on the estimation of times required for the attainment of equilibrium by noncooperative, single site ligand-receptor systemsCellular and Molecular Life Sciences, 1982
- Specificity of the Adrenal Steroid Receptor System in Rat Hippocampus*Endocrinology, 1982
- 17α-Alkynyl-11β,17-dihydroxyandrostane derivatives : A new class of potent glucocorticoids.Steroids, 1981
- Adrenal steroids and extinction behavior: Antagonism by progesterone, deoxycorticosterone and dexamethasone of a specific effect of corticosteroneLife Sciences, 1980
- Nuclear Progestin Receptors in Guinea Pig Brain Measured by anin VitroExchange Assay after Hormonal Treatments that Affect Lordosis*Endocrinology, 1980
- An exchange assay for estrogen receptors in cell nuclei of the adult rat brainSteroids, 1977
- PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENTJournal of Biological Chemistry, 1951